The major objective of this Phase I STTR grant is to evaluate the GI safety, therapeutic activity and stability of a new class of non-steroidal anti-inflammatory drugs (NSAIDs) that are formulated with a soy bean oil that is enriched in phosphatidylcholine (PC). This represents a second generation of PC-NSAIDs, developed by the PI and associates, that would have additional benefits with regards to cost and stability of the drug. The specific aims of this application are focused on confirming preliminary data that the oil-based PC-NSAIDs (and specifically PC-aspirin and PC-ibuprofen) possess low GI toxicity and enhanced therapeutic activity employing rodent models of acute and chronic NSAID-induced ulcer disease, and joint inflammation/pain. We also propose a series of in vivo and in vitro studies to define the molecular basis of the enhanced therapeutics of the PC-NSAIDs, evaluating the drugs' bioavailability, membrane permeability and cyclooxygenase (COX) inhibitory activity. In the last specific aim, we will evaluate the stability of PC-aspirin and PC-ibuprofen in the presence and absence of fluidizers and anti-oxidants in hard capsules employing an encapsulation technique that would limit the NSAIDs' exposure to water, which is particularly critical for aspirin. The above studies will provide us with important information required for the initiation of clinical trials and commercialization of PC-NSAIDs.